HIV immunization programmes will only be effective if sufficient numbers of persons accept the vaccine. Our aims were to evaluate HIV vaccine acceptability among adolescents and to examine how vaccine characteristics influence acceptability. We recruited 661 adolescents from community health clinics in Indianapolis, Indiana, USA to complete either written or computerized questionnaires, both of which assessed HIV vaccine acceptability as a function of efficacy, cost, type of vaccine, mode of delivery, and parental permission for immunization (required or not required). For both the written and computer methods, efficacy had the strongest effect on acceptability, followed by type of vaccine and cost. Low efficacy, high cost, and live-attenuated vaccines were associated with lower acceptability. These findings suggest that as efforts to develop HIV vaccines continue, it will be important, in parallel, to anticipate potential obstacles to vaccine acceptance, including the belief that a less efficacious HIV vaccine is unacceptable.